1. Field of the Invention
This invention relates to new and improved apparatus and method for the substantial separation and/or formation of immiscible liquid streams on a continuous flow basis; and which are particularly adapted to use in automated, continuous flow sample liquid analysis systems to maximize the accuracy of the sample liquid analysis results.
2. Description of the prior art
Although a number of methods and apparatus are known for the separation of sample liquids from immiscible isolation liquids within which the same are encapsulated for minimization of sample liquid carryover attendant sample liquid analysis, these will generally be found to rely primarily upon the natural separational effects of the differences in specific gravity between those liquids; and thus will not be found effective to accomplish the virtually immediate, and complete in terms of totally distinct locations of the thusly separated liquids, substantial separation of the liquids on a continuous flow basis as inherently provided by the apparatus and method of this invention.
More specifically U.S. Pat. No. 4,121,466 issued Oct. 24, 1978 to Allen Reickler, et al for "Liquid Dispenser With An Improved Probe" and assigned to the assignee hereof, discloses the use of an immiscible hydrophobic isolation liquid to encapsulate successive aqueous sample liquids for minimization of sample liquid carryover attendant sample liquid analysis. In this apparatus, wherein the isolation liquid is of greater density than the sample liquids, the former is simply allowed to settle out from the latter to the bottom of a reaction receptacle into which the isolation liquid-encapsulated sample liquids are dispensed, thereby leaving the sample liquid readily accessible for reaction with reagent liquids as may then be introduced into the receptacle. The settling out of the isolation liquid can and does take time and, in any event, leaves the thusly separated isolation and sample liquids in essentially the same location, e.g. the reaction receptacle.
In like manner, U.S. Pat. No. 4,357,301 issued Nov. 2, 1982 to Michael M. Cassaday, et al for "Reaction Cuvette" and assigned to the assignee hereof, also discloses the use of an immiscible isolation liquid to encapsulate successive aqueous sample liquids for minimization of sample liquid carryover attendant sample liquid analysis. In this apparatus wherein the isolation liquid is again hydrophobic and apparently of greater density than the sample liquids, sharp projections or the like of a hydrophilic material are provided at the bottom of the reaction cuvette, and operate to puncture the isolation liquid-encapsulated sample liquids as the same are introduced into the cuvette; thereby freeing for reaction the sample liquids from the isolation liquid which simply floats to the top of the cuvette. Again, this separation can and does take time, and in any event, leaves the isolation and sample liquids in essentially the same location, e.g. the reaction cuvette.
Under the circumstances, it has been determined by applicants that the continued presence of the "separated" isolation liquid with the sample liquid at the same location can and does present significant problems with regard to the accuracy of subsequent sample liquid analysis results; and especially in those instances wherein those sample liquid analysis results are arrived at through use of sample liquid analysis methodologies involving, for example, reflectance spectroscopy, ion selective electrodes, colorimetry, cell counting and or enzyme coil operation.
Hydrophobic filtration, for example as disclosed by the "nonwet" filter in U.S. Pat. No. 4,266,559 issued May 12, 1981 for David S. Akhavi for "Blood Sampler," wherein a filter of hydrophobic material is used to prevent the escape of an aqueous sample liquid from a collection device while permitting the passage of air therethrough to enable filling of the device, is also known in the prior art, but is clearly totally irrelevant to the substantial separation of immiscible liquids from a flowing stream to distinct locations on a continuous flow basis.
Also of limited relevance to liquid separation are conventional debubbler devices as have now become standard in continuous flow sample liquid analysis systems and which operate to remove the air segments from a continuously flowing, air segmented sample liquid stream prior to sample liquid analysis. These debubbler devices, which operate primarily on the very significant differences in specific gravity between air and the sample liquids of interest are clearly totally inapplicable to the effective substantial separation of immiscible liquids on a continuous flow basis.
With regard to immiscible liquid stream formation, it is known in the prior art to form immiscible liquid streams on a continuous flow basis by the essentially concomitant introduction of aqueous sample liquids, and a hydrophobic isolation liquid which is immiscible therewith, into a hydrophobic flow conduit which is selectively "wettable" by the isolation liquid to the substantial exclusion of the aqueous sample liquids, thereby essentially encapsulating the former in a layer of the latter and effectively minimizing aqueous sample liquid carryover.
More specifically, in most instances, this will be seen to be accomplished by the concomitant aspiration of the aqueous sample liquids and the immiscible isolation liquid into the sample analysis system by the sample aspirating probe as disclosed, for example, in U.S. Pat. No. 4,121,466 as discussed hereinabove, and in each of the U.S. Pat. No. 4,253,846 issued Mar. 3, 1981 to William J. Smythe, et al for "Method and Apparatus for Automated Analysis of Fluid Samples," and assigned to the assignee hereof, and U.S. Pat. No. 4,517,302 issued May 14, 1986 to Steven Saros, et al for "Sample Analysis System," and also assigned to the assignee hereof. Although prior art apparatus of this nature do operate to satisfactorily continuously form the isolation liquid layer-encapsulated, sample liquid stream, the same are of course limited in location to the aspirating probe at the entry point of the analysis system without the system flow conduit, thereby limiting the versatility thereof. In addition, since these prior art apparatus are strictly tied into the operation of the analysis system aspirating probe, satisfactory operation thereof by definition requires the use of moving parts which can prove somewhat problematical. Also, the extremely high speeds of operation of contemporary sample liquid analysis systems of the nature here under discussion require extremely high speeds of aspiration probe movement through decidedly limited distances, and these requirements can adversely affect the satisfactory formation of the isolation liquid layer by the probe.
U.S. Pat. No. 3,479,141 issued Nov. 18, 1969 to William J. Smythe, et al, and now expired, for "Method and Apparatus for Analysis," and assigned to the assignee hereof, discloses the formation on a continuous flow basis of an isolation liquid layer encapsulated sample liquid stream by the concomitant pumping through separate compressible pump tubes of a peristaltic pump of immiscible isolation and buffer liquids to a tube junction for merger therein and flow therefrom through the recipient side of a dialyzer to acquire the sample liquids for subsequent flow of the thusly isolation liquid encapsulated sample liquid stream through a glass conduit to a hydrophobic conduit for additional sample liquid processing. Formation of the isolation liquid-encapsulated sample liquid stream in this manner of necessity results in an extremely "rich" isolation liquid layer, to very significant economic disadvantage as made clear by FIG. 1 of the drawing of that patent; and operates to effectively minimize sample liquid carryover only upon the arrival of the stream at the hydrophobic conduit. In addition, formation of the isolation liquid-encapsulated sample liquid stream in this manner is, of course, unduly complex, and simply cannot in any event provide the precision of isolation liquid layer formation as required by more contemporary, highly technically sophisticated continuous flow sample liquid analysis systems.
U.S. Pat. No. 3,726,297 issued Apr. 10, 1973 to Richard H. Heimann, Aaron Kassel and Donald F. Kopelman for "Method And Device For Introducing For Mixing A First Liquid Into A Second Liquid," and assigned to the assignee hereof, discloses a tube disposed within an elongated passageway in which a first liquid is flowing for introducing a second liquid thereinto for mixture with said first liquid. In this device, the first and second liquids are, of course, not immiscible; and the second liquid is introduced into the first liquid in the countercurrent direction relative to the flow of the latter Accordingly, it will be immediately clear to those skilled in this art that the device of U.S. Pat. No. 3,726,297 is totally inapplicable to the formation of an isolation liquid-encapsulated sample liquid stream from immiscible isolation and sample liquids in a conduit which is selectively "wettable" by the isolation liquid to the substantial exclusion of the sample liquid.